A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).
A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).
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GATA3附近的一种遗传变异，涉及良性前列腺增生（BPH）和较低尿路症状（LUTS）的遗传易感性和病因。
DOI：
10.1002/pros.23380
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Na R;Helfand BT;Chen H;Conran CA;Crawford SE;Hayward SW;Tammela TLJ;Hoffman-Bolton J;Zheng SL;Walsh PC;Schleutker J;Platz EA;Isaacs WB;Xu J
良性前列腺增生（BPH）和相关的下尿路症状（LUTS）是常见的疾病。除了研究表明有大量的遗传成分外，对其病因知之甚少。我们的目标是提供一个全面的，全基因组的评估遗传风险和可能的病因机制，在前列腺增生症。我们对来自三个独立人群、度他雄胺减少前列腺癌事件（REDUCE）试验、CLUE II队列和芬兰医院人群的男性进行了一项三阶段全基因组关联研究（GWAS）。在REDUCE和CLUE II中使用Illumina HumanOmniExpress BeadChip对DNA样品进行基因分型，并在芬兰人群中使用Sequenom iPLEX系统进行确认阶段。Logistic回归模型用于评估每个SNP与BPH/LUTS之间的关联。在两个GWAS（CLUE II和REDUCE）的荟萃分析中，14个SNP达到P <5.0 × 10 − 4。共选择773个SNP用于完成队列中的确认步骤。只有一个位于GATA 3下游约489kb的SNP（rs17144046）在多重检验校正后仍然显著（P <6.5 × 10 − 5）。在对三个阶段进行荟萃分析后，该SNP略微达到了GWAS显著性水平（P-meta = 8.89 × 10 - 7）。表达数量性状基因座（eQTL）分析显示rs17144046的危险等位基因（G）与GATA 3的表达显著相关（P = 0.017）。研究表明GATA 3与BPH的发病和进展密切相关。在三个独立人群中，位于GATA 3附近的Rs17144046与BPH/LUTS显著相关，但未达到严格的GWAS显著性水平。GATA 3基因变异可能在BPH/LUTS的遗传易感性和病因学中发挥作用。需要在这一领域开展进一步研究。
Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common conditions. Little is known about their etiologies except that studies have suggested a substantial heritable component. Our objective is to provide a comprehensive, genome-wide evaluation of inherited risks and possible mechanisms of etiology in BPH. We performed a three-stage, genome-wide association study (GWAS) of men from three independent populations, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, the CLUE II cohort, and a Finnish hospital-based population. DNA samples were genotyped using the Illumina HumanOmniExpress BeadChip in REDUCE and CLUE II, and using the Sequenom iPLEX system for the confirmation stage in the Finnish population. A logistic regression model was used to evaluate the association between each SNP and BPH/LUTS. Fourteen SNPs reached P<5.0×10−4 in the meta-analysis of the two GWASs (CLUE II and REDUCE). A total of 773 SNPs were chosen for the confirmation step in the Finish cohort. Only one SNP (rs17144046) located ~489kb downstream of GATA3 remained significant after correction for multiple testing (P<6.5×10−5). This SNP marginally reached the GWAS significance level after performing a meta-analysis of the three stages (P−meta=8.89×10−7). Expression quantitative trait loci (eQTL) analyses showed that the risk allele (G) of rs17144046 was significantly associated with increased expression of GATA3 (P=0.017). Reported studies indicated a close correlation between GATA3 and BPH pathogenesis and progression. Rs17144046 located near GATA3 was significantly associated with BPH/LUTS in three independent populations, but did not reach a stringent GWAS significance level. Genetic variants of GATA3 may play a role in the inherited susceptibility and etiology of BPH/LUTS. Further research in this area is needed.
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影响因子：
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作者：
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通讯作者：
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